Tear osmolarity and tear film parameters in patients with ocular rosacea

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A

RTICLE

Tear Osmolarity and Tear Film Parameters in Patients With

Ocular Rosacea

Sevil Karaman Erdur,

M.D.

, Mustafa Eliacik,

M.D.

, Mehmet Selim Kocabora,

M.D.

, Ali Balevi,

M.D.

,

Goktug Demirci,

M.D.

, Mustafa Ozsutcu,

M.D.

, Gokhan Gulkilik,

M.D.

, and Cengiz Aras,

M.D.

Objectives: The aim of this study was to evaluate tear osmolarity and tear film parameters in patients with ocular rosacea.

Methods: In a single center, 25 eyes of 25 patients with ocular rosacea (group 1), 25 eyes of 25 patients with rosacea without ocular involvement (group 2), and 20 eyes of 20 healthy individuals (group 3) were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I

test, tearfilm break-up time (TBUT), scoring of ocular surface fluorescein

staining using modified Oxford scale, and tear osmolarity.

Results: Tear osmolarity values, OSDI and Oxford scale scores were

significantly higher in group 1 than in groups 2 and 3 (P,0.001 for all).

Schirmer I test and TBUT in group 1 were significantly lower than in

groups 2 and 3 (P,0.001 for all). There were no significant differences

in OSDI, Schirmer I test, TBUT, Oxford scores, or tear osmolarity between

groups 2 and 3 (P¼0.629, P¼0.175, P¼0.713, P¼865, and P¼0.388,

respectively).

Conclusions: This study showed that ocular rosacea is associated with tear

hyperosmolarity and tearfilm dysfunction.

Key Words: Dry eye—Ocular surface—Meibomian gland dysfunction—

Tear osmolarity—Ocular rosacea.

(Eye & Contact Lens 2016;42: 347–349)

R

osacea, which primarily affects blood vessels and piloseba-ceous units of the central facial skin (i.e., cheeks, chin, nose, and central forehead), is a chronic cutaneous disorder.1_{The most}

common clinicalfindings are transient or persistent erythema, tel-angiectasias, papules, pustules, and phymatous changes.2

Rosacea also causes eyelid and ocular surface inflammation and may involve the eyes in 58% to 72% of patients.3

Ocular rosacea may present with a watery or bloodshot appearance (interpalpebral conjunctival hyperemia), foreign body sensation, burning or stinging, dryness, itching, light sensitivity, blurred vision, telangiectasias of the conjunctiva and lid margin, and lid and periocular erythema. Anterior blepharitis, meibomian gland dysfunction, and eyelid margin irregularity may also be seen.2–5

Insufficient tear production or excessive tear evaporation both cause tear hyperosmolarity.6

The most common cause of increased evaporation is meibomian gland disease (MGD), which results in reduced oil delivery to the lid margin and tear film.7

Individuals with MGD may also have hypersecretion of meibum. Some per-sons with ocular rosacea may actually have hypersecretory MGD. Abnormal meibum composition may also play a role in accelerated tear evaporation. Hyperosmolarity has been shown to provide pro-inflammatory stress to the ocular surface.8

Some studies suggest that tear osmolarity measurement should be preferred over alterna-tive subjecalterna-tive means as the gold standard to diagnose dry eye disease.9_{Despite its well-established importance, technology with}

good sensitivity and specificity to measure tear osmolarity in the evaluation of dry eye disease has only recently become available.10,11

The aim of our study was to evaluate tear osmolarity and other ocular surface parameters in subjects with ocular rosacea and to compare the results with those of subjects with rosacea without ocular involvement and with healthy controls.

MATERIALS AND METHODS

A total of 25 eyes of 25 patients with ocular rosacea (group 1), 25 eyes of 25 patients with rosacea without ocular involvement (group 2), and 25 eyes of 25 healthy individuals without signs or symptoms of dry eye disease or other ocular pathology (group 3) were included in this single-center, cross-sectional observational study. Right eye data for each patient were assessed.

Patients in groups 1 and 2 were diagnosed with rosacea by a specialist dermatologist (A.B.). Among those diagnosed with rosacea, ocular rosacea was diagnosed on detection of one or more of the following: watery or bloodshot appearance, foreign body sensation, burning or stinging, dryness, itching, light sensitivity, blurred vision, telangiectasias of the conjunctiva and lid margin, lid and periocular erythema, anterior blepharitis, MGD, or irregularity of eyelid margins.12

Subjects were excluded if they had a history of smoking, current or recent drug use that could affect the lacrimal functional unit, active ocular infection or allergy, ocular surface scarring, previous eye surgery, or current contact lens use.

The study was reviewed and approved by the Istanbul Medipol University Ethics Committee, and written informed consent was obtained from each patient before enrollment. The study was conducted in accordance with the tenets of the Declaration of Helsinki.

Initially, patients completed the International Ocular Surface Disease Index (OSDI) survey. All subjects underwent a full

From the Departments of Ophthalmology (S.K.E., M.E., M.S.K., G.D., M.O., G.G., C.A.) and Dermatology (A.B.), Istanbul Medipol University, Medicine School, Istanbul, Turkey.

The authors have no funding or conflicts of interest to disclose.

Address correspondence to Sevil Karaman Erdur, M.D., Department of Ophthalmology, Istanbul Medipol University, Medicine School, Istanbul 34214, Turkey; e-mail: karamansevil@gmail.com

Accepted September 14, 2015. DOI: 10.1097/ICL.0000000000000211

Eye & Contact Lens  Volume 42, Number 6, November 2016 ₃₄₇

ophthalmological examination in the same order, including visual acuity assessment, standardized slitlamp examination, and fundus examination. Full ophthalmologic examination and evaluation of tear osmolarity were performed on the same day but at a different time.

Tear osmolarity measurements were evaluated using a TearLab osmometer (TearLab Co., San Diego, CA). Tears were collected from the inferior lateral tear meniscus. Three consecutive measure-ments were obtained, and their mean was used for statistical analysis. All eyes underwent cornealfluorescein staining scoring using the Oxford scheme.

Tearfilm break-up time (TBUT) was assessed after instillation of 2% fluorescein staining under a cobalt blue filter. The time interval between the last complete blink and the appearance of the first dry spot was recorded. The mean of three consecutive measurements was obtained. The Schirmer I test was performed with topical anesthesia using a standardizedfilter strip (Bio-Tech Vision Care, Ahmedabad, India). The amount of wetting was measured after 5 min.

The normality of the distribution of each of the parameters was checked using the Kolmogorov–Smirnov normality test. The tear osmolarity, Schirmer I test with anesthesia, TBUT values and OSDI scores among groups were compared using one-way analysis of var-iance. The differences were calculated using the multiple comparison Tukey’s test. A P-value ,0.05 was considered statistically significant.

RESULTS

The mean subject age was 46.768.5 years (range: 35–63 years) in group 1 (14 women and 11 men), 48.8610.3 years (range: 32– 69 years) in group 2 (12 women and 13 men), and 47.1610.1 years (range: 33–63 years) in group 3 (13 women and 12 men). There were no significant differences among the three groups with respect to age or sex (P¼0.72 and P¼0.852, respectively). Summary sta-tistics are shown in Table 1. The mean tear osmolarity was signif-icantly higher in group 1 compared with groups 2 and 3 (P,0.001 for both). There was no significant difference in tear osmolarity between groups 2 and 3 (P¼0.388).

The Schirmer I test values for group 1 were significantly lower than those for groups 2 and 3 (P,0.001 for both). There was no significant difference in Schirmer I test results between groups 2 and 3 (P¼0.175). Tear film break-up time measurements for group 1 were significantly lower than those for groups 2 and 3 (P,0.001 for both). Tear film break-up time measurements did not differ between groups 2 and 3 (P¼0.713).

The mean superficial punctate staining, as measured by the Oxford scale, differed significantly between group 1 and group 2, and between group 1 and group 3 (P¼0.016 and P¼0.004, respec-tively). There was no significant difference between groups 2 and 3 on the Oxford scale (P¼0.865). The mean OSDI scores were

significantly higher in group 1 than in groups 2 and 3 (P,0.001 for both). No significant difference in OSDI score was noted between groups 2 and 3 (P¼0.86).

DISCUSSION

In this study, patients with ocular rosacea had significantly higher tear osmolarity levels, lower Schirmer I scores, and lower TBUT values than patients with rosacea without ocular involve-ment and controls. There was no difference between the patients with rosacea without ocular involvement and control patients.

Zengin et al.13_{compared 28 patients with ocular rosacea with 15}

patients with dermatologic rosacea and their sex- and age-matched control subjects. They found that patients with ocular rosacea had significantly lower Schirmer I scores, TBUT, and meibomian gland function values than for those with cutaneous-limited rosacea and controls. Consistent with our study, they reported that test results for patients with dermatologic rosacea did not differ from those of age- and sex-matched controls. A study by Yaylali et al.14_showed

higher rose Bengal staining scores, lower TBUT values and lower Schirmer I test values for those with ocular rosacea than for pa-tients in the control group. Kocak-Altintas et al.15

found that pa-tients with ocular rosacea had both decreased tear production and increased tear instability.

Based on the results of this study, we suggest that the tear hyperosmolarity believed to be the main pathogenic factor leading to ocular surface inflammation may decrease the number of goblet cells and alter ocular surface mucins to cause tear film instabil-ity.9,16

This instability may trigger a cycle that perpetuates the inflammatory process.

Barton et al.17

found a differential increase in the level of the inflammatory cytokine interleukin 1a in the tear fluid from patients with ocular rosacea compared with controls. They hypothesized two possible causes: (1) increased production or release by epithe-lial or inflammatory cells on the ocular surface or both; and (2) reduced tear drainage. Activation of the epithelial signaling mole-cules cascade induces damage to surface epithelium, release of pro-inflammatory mediators into tears, and cell death by apoptosis.

In this study, we found that patients with ocular rosacea have different tear film parameters compared with those with rosacea without ocular involvement and controls. Patients with ocular rosacea had dry eye symptoms but were unaware of a connection between their ocular symptoms and rosacea. Although patients with rosacea without ocular involvement also had elevated tear osmolarity values compared with controls, the difference was not statistically significant. This finding is remarkable because MGD, which causes evaporative dry eye, is present in up to of 92% of patients with rosacea.4,18

It is common for patients with rosacea not to mention ocular symptoms in a dermatology clinic unless they are

TABLE 1. Comparisons of the Mean Dry Eye Parameters Among Groups

Parameter Group 1 Group 2 Group 3 P

Tear osmolarity, mean6SD, mOsm/L 321616.3 295.8619.5 286.3623.4 ,0.001 (group 1 vs. groups 2 and 3) Schirmer test, mean6SD, mm 10.563.2 18.364.7 20.464.2 ,0.001 (group 1 vs. groups 2 and 3) Oxford scale, mean6SD 0.5660.7 0.1260.33 0.0460.2 0.016 (group 1 vs. group 2); 0.004 (group 1 vs. group 3) TBUT, mean6SD, sec 9.863.5 21.664.3 22.564 ,0.001 (group 1 vs. groups 2 and 3) OSDI score, mean6SD 54.1616.5 24.5617.3 22.3611.6 ,0.001 (group 1 vs. groups 2 and 3)

OSDI, ocular surface disease index; SD, standard deviation; TBUT, tear film break-up time.

S. Karaman Erdur et al. Eye & Contact Lens  Volume 42, Number 6, November 2016

348 Eye & Contact Lens  Volume 42, Number 6, November 2016

directly questioned. Therefore, we strongly encourage dermatolo-gists to assess patients for ocular symptoms.

A major limitation of our study is that we were unable to perform further tests, including assessment of changes in mean goblet cell density, conjunctival impression cytology, and espe-cially meibography. Further evaluation using these measures may provide more information about the relationship between ocular rosacea and dry eye disease.

In conclusion, this study showed that patients with ocular rosacea had higher osmolarity than patients with rosacea without ocular involvement and healthy individuals. They also had tear film dysfunction. Prospective studies are needed to evaluate the changes in tear function and dry eye disease during the course of ocular rosacea.

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